NORCURON

Main information

  • Trade name:
  • NORCURON 4mg powder for injection ampoule
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • NORCURON 4mg powder for injection ampoule
    Australia
  • Language:
  • English

Status

  • Source:
  • Dept. of Health,Therapeutic Goods Administration - Australia
  • Authorization number:
  • 177718
  • Last update:
  • 14-11-2017

Public Assessment Report

Public Summary

Summary for ARTG Entry:

177718

NORCURON vecuronium bromide 4mg powder for injection ampoule

ARTG entry for

Medicine Registered

Sponsor

Merck Sharp & Dohme (Australia) Pty Ltd

Postal Address

North Ryde Post Business Centre,Locked Bag 2234,NORTH RYDE BC, NSW, 1670

Australia

ARTG Start Date

6/01/2011

Product category

Medicine

Status

Active

Approval area

Drug Safety Evaluation Branch

Conditions

Conditions applicable to the relevant category and class of therapeutic goods as specified in the document "Conditions Applying to Therapeutic Goods

Accepted for Registration or Listing as Goods Currently Supplied at the Commencement of the Therapeutic Goods Act 1989"

Conditions applicable to all therapeutic goods as specified in the document "Standard Conditions Applying to Registered or Listed Therapeutic Goods

Under Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Conditions applicable to the relevant category and class of therapeutic goods as specified in the document "Standard Conditions Applying to Registered

or Listed Therapeutic Goods Under Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Products

1. NORCURON 4mg powder for injection ampoule

Product Type

Single Medicine Product

Effective date

24/09/2014

Warnings

See Product Information and Consumer Medicine Information for this product

Standard Indications

Specific Indications

Norcuron is a skeletal muscle relaxant for use as an adjunct to general anaesthesia in adults and children for all surgical processes.

Additional Product information

Container information

Type

Material

Life Time

Temperature

Closure

Conditions

Ampoule

Glass Type I Clear

3 Years

Store below 25

degrees Celsius

Not recorded

Protect from Light

Pack Size/Poison information

Pack Size

Poison Schedule

10 ampoules of powder - 4mg

(S4) Prescription Only Medicine

Components

1. powder for injection

Dosage Form

Injection, powder for

Route of Administration

Intravenous

Visual Identification

White powder

Active Ingredients

Vecuronium bromide

4 mg

© Commonwealth of Australia.This work is copyright.You are not permitted to re-transmit, distribute or commercialise the material without obtaining prior

written approval from the Commonwealth.Further details can be found at http://www.tga.gov.au/about/website-copyright.htm.

Public Summary

Page 1 of

Produced at 29.11.2017 at 11:05:23 AEDT

This is not an ARTG Certificate document.

The onus is on the reader to verify the current accuracy of the information on the document subsequent to the date shown.

Visit www.tga.gov.au for contact information

Summary of Product characteristics: dosage, interactions, side effects

RA 8720 AU S4 (REF 4.0) A140814 V3

PRODUCT INFORMATION

NORCURON

®

(vecuronium bromide)

NAME OF THE MEDICINE

- Non-proprietary Name:

Vecuronium bromide

- Laboratory Code:

Org NC 45

- Molecular Structure:

Mol. Formula: C

34

H

57

BrN

2

O

4

Mol. Weight: 637.73

Chemical Name:

1-[3

,17

-diacetoxy-2

-(piperidin-1-yl)-5

-androstan-16

-yl]

-1-methylpiperidinium bromide

DESCRIPTION

Vecuronium bromide is a monoquaternary steroid derivative homologous with pancuronium

bromide.

It is an odourless, bitter tasting white to creamy white, microcrystalline powder. At 25

C (pH

3), its solubility is 16 mg/mL, and pKa is 8.97. Because vecuronium bromide hydrolyses

rapidly in water, a ready-for-use aqueous solution form is not available.

Following reconstitution with solvent (Water for Injections) the resultant solution is isotonic

and has a pH of 4. Norcuron is available in ampoules and vials containing 4 mg and 10 mg

of vecuronium bromide, respectively. Each ampoule or vial also contains citric acid, sodium

phosphate, sodium hydroxide and/or phosphoric acid to buffer and adjust the pH and

mannitol to make isotonic.

PHARMACOLOGY

Pharmacodynamics

Norcuron is a nondepolarising neuromuscular blocking agent possessing all of the

characteristic pharmacological actions of this class of drugs (curariform). It acts by

competing for cholinergic receptors at the motor end-plate. The antagonism to acetylcholine

RA 8720 AU S4 (REF 4.0) A140814 V3

is inhibited and neuromuscular block is reversed by acetylcholinesterase inhibitors such as

neostigmine, edrophonium and pyridostigmine. The neuromuscular block can also be

reversed by sugammadex, a Selective Relaxant Binding Agent. The potency of Norcuron is

equal to or somewhat greater than that of pancuronium; the duration of neuromuscular

blockade produced by Norcuron is significantly shorter than that of pancuronium at initially

equipotent doses with less cumulative effect. The time to onset of paralysis decreases and

the duration of maximum effect increases with increasing Norcuron doses. The use of an

appropriate neuromuscular monitoring technique may be of benefit in assessing the degree

of muscular relaxation.

An initial Norcuron dose of 0.10 mg/kg generally produces first depression of twitch in

approximately 1 minute, good or excellent intubation conditions within 2.5 to 3 minutes and

maximum neuromuscular blockade within 3 to 5 minutes of injection in most patients.

Because of the minimal tendency for cumulation, frequent maintenance doses can be given

in succession. Norcuron is suitable for both short and prolonged operations.

At the clinical dosage, vecuronium bromide has no vagolytic or ganglion blocking actions and

histamine release is not expected to be clinically significant. Therefore side-effects on the

cardiovascular and pulmonary systems are not to be expected. It does not counteract those

haemodynamic changes or known side effects produced by or associated with anaesthetic

agents and the likelihood of reflex bradycardia may thus be increased. It has no known

effect on consciousness, the pain threshold or cerebration.

The action of vecuronium bromide can be antagonised either by sugammadex or by

acetylcholinesterase inhibitors, such as neostigmine, pyridostigmine or edrophonium, in

appropriate dosage. Sugammadex can be given for routine reversal at 1-2 post-tetanic

counts to reappearance of T

. Acetylcholinesterase inhibitors can be administered at

reappearance of T

or at the first signs of clinical recovery.

Paediatric Patients

Infants: The ED

dose of Norcuron under nitrous oxide in oxygen anaesthesia was found to

be approximately the same (approx. 47

g/kg body weight) as in adults. The onset of time is

considerably shorter in infants as compared to children and adults, probably due to the

shorter circulation time and relatively large cardiac output. Also, greater sensitivity of the

neuromuscular junction to the action of neuromuscular blocking agents in these patients may

account for a more rapid onset of action.

The duration of action and recovery time with Norcuron is longer in infants than in adults.

Maintenance doses of Norcuron should therefore be less frequently administered (See also

Precautions, Use in Infants and Dosage and Administration).

Children: The ED

dose of Norcuron under nitrous oxide in oxygen anaesthesia was found

to be higher than in adults (0.081 vs 0.043 mg/kg body weight, respectively). In comparison

to adults, the duration of action and recovery time with Norcuron in children are in general

approximately 30% and 20-30% shorter, respectively.

Similar to adults, cumulative effects with repeat maintenance doses of approximately one

quarter of the initial dose and administered at 25% recovery control twitch height are not

observed in paediatric patients.

Pharmacokinetics

After intravenous administration of 0.1 – 0.15 mg/kg vecuronium, the distribution half –life of

vecuronium amounts to 1.2 – 1.4 minutes. Vecuronium is mainly distributed in the

extracellular fluid compartment. At steady state, the volume of distribution is 0.16 - 0.51

L.kg

in adult patients.

RA 8720 AU S4 (REF 4.0) A140814 V3

The plasma clearance of vecuronium amounts to 3.0 – 5.6 mL.kg

.min

and its plasma

elimination half-life is 36 – 117 minutes.

The extent of metabolism of vecuronium is relatively low. In humans, a 3-hydroxy derivative

having approximately 50% less neuromuscular blocking potency than vecuronium is formed

in the liver. In patients not suffering from renal or hepatic failure, the plasma concentration

of this derivative is low, and does not contribute to the neuromuscular block occurring after

administration of Norcuron.

Biliary excretion is the main elimination route. It is estimated that within 24 hours after

intravenous administration of Norcuron, 40 to 60% of the dose administered is excreted into

the bile as monoquaternary compounds. Approximately 95% of these monoquaternary

compounds is unchanged vecuronium and less than 5% is 3-hydroxy vecuronium.

Prolonged duration of action has been observed in patients with liver disease and/or biliary

tract disease, probably as a result of decreased clearance leading to an increased

elimination half-life.

Renal elimination is relatively low. The amount of monoquaternary compounds excreted in

the urine collected by intravesical catheter for 24 hours following Norcuron administration is

20 – 30% of the dose administered. In patients with renal failure, the duration of action may

be prolonged. This is probably the result of a reduced plasma clearance.

INDICATIONS

Norcuron is a skeletal muscle relaxant for use as an adjunct to general anaesthesia in adults

and children for all surgical procedures.

CONTRAINDICATIONS

Norcuron is contraindicated in patients known to be hypersensitive to any of its components

including the bromide ion.

Warning

Since Norcuron causes paralysis of the respiratory muscles, ventilatory support is mandatory

for patients treated with this drug until adequate spontaneous respiration is restored.

PRECAUTIONS

General

1) Anaphylactic reactions

Anaphylactic reactions can occur following the administration of neuromuscular blocking

agents. Allergic cross-reactivity between muscle relaxants has been reported.

2) Histamine release and histaminoid reactions

Since neuromuscular blocking agents are known to be capable of inducing histamine release

both locally at the site of injection and systemically, the possible occurrence of itching and

erythematous reactions at the site of injection and/or generalised histaminoid (anaphylactoid)

reactions (see Adverse Reactions) should always be taken into consideration when

administering these drugs. Experimental studies with intradermal injection of Norcuron have

demonstrated that this drug has only a weak capacity for inducing local histamine release.

Controlled studies in man failed to demonstrate any significant rise in plasma levels after

intravenous administration of Norcuron. Such cases have been reported only rarely, despite

the fact that Norcuron is now widely used.

RA 8720 AU S4 (REF 4.0) A140814 V3

3) Cardiovascular effects

Since Norcuron has no cardiovascular effects within the clinical dose range, it does not

attenuate bradycardia that may occur due to the use of some types of anaesthetics and

opiates or due to vagal reflexes during surgery. The dosage or need for vagolytic drugs may

thus be increased in such circumstances.

4) As with other neuromuscular blocking agents, residual curarization has been reported for

Norcuron. Factors which could cause residual curarization after extubation in the post-

operative phase (such as drug interactions or patient condition) should also be considered. If

not already used as part of usual clinical practice, the use of sugammadex or another

reversal agent should be considered, especially in those cases where residual curarization is

more likely to occur.

Effects on fertility

No adverse effects on fertility or overall reproductive performance were observed in rats

treated with intravenous vecuronium bromide at doses up to 15% of the clinical dose on a

body surface area basis. Studies with vecuronium bromide alone or in combination with an

anaesthetic agent, at doses comparable with clinical dosages, have not been conducted.

Use in Pregnancy

Category C

Vecuronium crosses the placenta but there have been no demonstrated adverse effects in

the foetus or the newborn infant. In animal studies intravenous administration of vecuronium

bromide to rats during the period of organogenesis at up to maternotoxic doses (about 15%

of the recommended clinical dose, based on body surface area basis) was associated with

slightly increased incidences of visceral abnormalities. Similar administration to rabbits at

less than maternotoxic doses (about 0.5 - 2% of the recommended clinical dose, based on a

body surface area) was also associated with increased incidences of visceral abnormalities.

There are insufficient data on the use of Norcuron during animal or human pregnancy to

assess potential harm to the foetus. Norcuron should be given to a pregnant woman only

when the attending physician decides that the benefits outweigh the risks.

Note: Reversal of Norcuron-induced neuromuscular block may be unsatisfactory in patients

receiving magnesium salts for the management of toxemia of pregnancy because

magnesium salts enhance the neuromuscular blockade (see Drug Interactions). In patients,

the dosage of Norcuron should be reduced and carefully titrated to twitch response.

Caesarean section

Studies with Norcuron, administered in doses up to 0.1 mg/kg, have shown its safety for use

in caesarean section.

In several clinical studies Norcuron did not affect Apgar score, foetal muscle tonus or

cardiorespiratory adaptation. From umbilical cord blood sampling it is apparent that only very

little placental transfer of Norcuron occurs, the amount being dependent on time from

injection to delivery, and which did not lead to the observation of any clinical adverse effect in

the new-born.

Use in Lactation

There are no human data on the use of Norcuron during lactation. A decrease in early

postnatal survival was observed in rats at a maternal dose of about 15% of the clinical dose,

based on body surface area. Norcuron should be given to lactating women only when the

attending physician decides that the benefits outweigh the risks.

RA 8720 AU S4 (REF 4.0) A140814 V3

Paediatric use

A variable, often prolonged, duration of action and potency has been observed in infants.

Infants under 1 year of age but older than 7 weeks are moderately more sensitive to

Norcuron on a mg/kg basis than adults and take about 1

times as long to recover (with or

without halothane anaesthesia). Use of Norcuron should therefore be avoided unless the

expected benefits outweigh the potential risks (See also Indications).

Use in Neuromuscular Syndromes

Extreme caution should be exercised and very small doses used in patients with myasthenia

gravis or myasthenic (Eaton-Lambert) syndrome. In such patients, an appropriate

neuromuscular monitoring technique and use of a small test dose may be of value in

monitoring the response to administration of muscle relaxants. In cases of neuromuscular

disease or after poliomyelitis, similar caution should be exercised.

Hepatic and/or Biliary Tract Disease and/or Renal Failure/Disease

Since vecuronium is excreted in bile and urine, Norcuron should be used with caution in

patients with clinically significant hepatic and/or biliary diseases and/or renal failure. In these

patient groups prolongation of action has been observed, especially when high doses of

vecuronium (0.15 – 0.2 mg/kg bodyweight) were administered in patients with hepatic

disease.

Altered Circulation Time

Conditions associated with slower circulation time in cardiovascular disease, old age and

oedematous states resulting in increased volume of distribution may contribute to a delay in

onset time. The duration of action may also be prolonged due to a reduced plasma

clearance. Therefore dosage should not be increased.

Disorders Due to Other Treatments/Conditions

Conditions which may increase the neuromuscular blocking effects of Norcuron are:

hypokalaemia (e.g. after severe vomiting, diarrhoea, and diuretic therapy),

hypermagnesaemia, hypocalcaemia (after massive transfusions), hypoproteinaemia,

dehydration, acidosis, hypercapnia, cachexia.

Electrolyte imbalance and diseases which lead to electrolyte imbalance, such as adrenal

cortical insufficiency, have been shown to alter neuromuscular blockade. Depending on the

nature of the imbalance, either enhancement or inhibition may be expected.

Severe electrolyte disturbances, altered blood pH or dehydration, should therefore be

corrected when possible, prior to administration of Norcuron. Monitoring of neuromuscular

block by nerve stimulator is useful in all severely ill patients.

Surgery Under Hypothermia

In operations under hypothermia, the neuromuscular blocking effect of Norcuron is increased

and the duration is prolonged.

Obesity

Like other neuromuscular blocking agents, Norcuron may exhibit a prolonged duration of

action and a prolonged spontaneous recovery in obese patients, when the administered

doses are calculated on actual body weight.

RA 8720 AU S4 (REF 4.0) A140814 V3

Burns

Patients with burns are known to develop resistance to non-depolarising agents. It is

recommended that the dose is titrated to response.

C.N.S.

Norcuron has no known effect on consciousness, the pain threshold or cerebration.

Administration must be accompanied by adequate anaesthesia or sedation.

I.C.U.

In general, following long term use of neuromuscular blocking agents in the ICU, prolonged

paralysis and/or skeletal muscle weakness has been noted. In order to help preclude

possible prolongation of neuromuscular block and/or overdosage it is strongly recommended

that neuromuscular transmission is monitored throughout the use of muscle relaxants. In

addition, patients should receive adequate analgesia and sedation. Furthermore, muscle

relaxants should be titrated to effect in the individual patients by or under supervision of

experienced clinicians who are familiar with their actions and with appropriate neuromuscular

monitoring techniques.

Myopathy, after long term administration of non-depolarising neuromuscular blocking agents

in the ICU in combination with corticosteroid therapy, has been reported frequently.

Therefore, for patients receiving both the neuromuscular blocking agents and corticosteroids,

the period of use of the neuromuscular blocking agent should be limited as much as

possible.

Effects on ability to drive and use machines

Since Norcuron is used as an adjunct to general anaesthesia, the usual precautionary

measures after general anaesthesia should be taken for ambulatory patients.

Carcinogenicity

Carcinogenicity studies with vecuronium have not been conducted.

Genotoxicity

Vecuronium was not genotoxic in a series of assays for gene mutation (Salmonella

typhimurium), chromosomal damage (rat micronucleus assay) or DNA damage.

Interactions with other medicines

The following drugs have been shown to influence the magnitude and/or duration of action of

non-depolarising neuromuscular blocking agents.

Effect of other drugs on Norcuron

Increased effect:

Halogenated volatile anaesthetics potentiate the neuromuscular block of Norcuron. The

effect only becomes apparent with maintenance dosing (see also Dosage and

Administration). With the presence of these volatile agents, reversal of the block with

anticholinesterase inhibitors could also be inhibited.

After intubation with suxamethonium (see Dosage and Administration).

RA 8720 AU S4 (REF 4.0) A140814 V3

Long-term concomitant use of corticosteroids and Norcuron in the ICU may result in a

prolonged duration of neuromuscular block or myopathy (see also Precautions and Adverse

Reactions).

Other drugs:

antibiotics: aminoglycoside, lincosamide and polypeptide antibiotics, acylamino-

penicillin antibiotics.

diuretics, quinidine, magnesium salts, calcium channel blocking agents, lithium salts,

cimetidine, lignocaine and acute administration of phenytoin or

-blocking agents.

Recurarization has been reported after post-operative administration of:

aminoglycoside, lincosamide, polypeptide and acylamino-penicillin antibiotics, quinidine and

magnesium salts (see Precautions).

Decreased effect (possible higher dose requirements)

Prior chronic administration of phenytoin or carbamazepine.

Variable effect

Administration of other non-depolarising neuromuscular blocking agents in combination with

Norcuron may produce attenuation or potentiation of the neuromuscular block, depending on

the order of administration and the neuromuscular blocking agent used.

Suxamethonium given after the administration of a non-depolarising neuromuscular blocking

agent may produce potentiation or attenuation of the neuromuscular blocking agent used.

Effect of Norcuron on other drugs

Norcuron combined with lignocaine may result in a quicker onset of action of lignocaine.

ADVERSE EFFECTS

Adverse Drug Reactions (ADRs) are rare (< 1/1000). The most commonly occurring ADRs

include changes in vital signs and prolonged neuromuscular block. The most frequently

reported ADR during post marketing surveillance is “anaphylactic and anaphylactoid

reactions” and associated symptoms (reporting frequency < 1/100 000). Please refer to

below table.

MedDRA SOC

Preferred term

Uncommon / rare

(<1/100, > 1/10 000)

Very rare (<1/10 000)

Immune system disorders

Hypersensitivity

Anaphylactic reaction

Anaphylactoid reaction

Anaphylactic shock

Anaphylactoid shock

Nervous system disorders

Flaccid paralysis

Cardiac disorder

Tachycardia

RA 8720 AU S4 (REF 4.0) A140814 V3

Vascular disorders

Hypotension

Circulatory collapse and shock

Flushing

Respiratory, thoracic and

mediastinal disorders

Bronchospasm

Skin and subcutaneous tissue

disorders

Angioneurotic oedema

Urticaria

Rash

Erythematous rash

Musculoskeletal and connective

tissue disorders

Muscular weakness

Steroid myopathy

General disorders and

administration site conditions

Drug ineffective

Decreased drug effect/ therapeutic

response

Increased drug effect / therapeutic

response

Face oedema

Injection site pain

Injection site reaction

Injury, poisoning and procedural

complications

Prolonged neuromuscular block

Delayed recovery from anaesthesia

Airway complication of

anaesthesia

MedDRA version 8

Frequencies are estimates derived from post-marketing surveillance reports and data from the general literature.

after long-term use in the ICU

Prolonged Neuromuscular Block

With non-depolarising agents in general, the most frequent adverse reactions consist of an

extension of the pharmacological action beyond the time period needed for surgery and

anaesthesia or inadequate reversal of the neuromuscular blockade. This may vary from

skeletal muscle weakness to profound and prolonged skeletal muscle paralysis resulting in

respiratory insufficiency or apnoea. A few cases of myopathy have been reported after

Norcuron was used in the ICU in combination with corticosteroids (see Precautions).

Inadequate reversal of the neuromuscular blockade is possible with Norcuron as with all

curariform drugs. These adverse reactions are managed by manual or mechanical

ventilation until recovery is judged adequate (See also Overdosage).

Anaphylactic reactions

Although very rare, severe anaphylactic reactions to neuromuscular blocking agents,

including Norcuron, have been reported. Anaphylactic/anaphylactoid reactions usually

comprise of several signs or symptoms, e.g. bronchospasm, cardiovascular changes (e.g.

hypotension, tachycardia, circulatory collapse – shock), and cutaneous changes (e.g.

angioedema, urticaria). These reactions have, in some cases, been fatal.

DOSAGE AND ADMINISTRATION

Norcuron should be administered in carefully adjusted dosage by or under the supervision of

experienced clinicians who are familiar with the action and use of these drugs. The drug

should not be administered unless facilities for intubation, artificial respiration, oxygen

therapy, suction and reversal agents are immediately available.

RA 8720 AU S4 (REF 4.0) A140814 V3

To avoid microbial contamination, Norcuron should be used without delay once reconstituted

and any residue should be discarded.

Reconstitution:

Norcuron 4mg: The contents of each ampoule of Norcuron 4mg should be dissolved in 1 mL

water for injections.

Norcuron 10mg: The contents of each vial should be dissolved in 5mL water for injections.

After reconstitution, Norcuron is administered intravenously either as a bolus injection or as a

continuous infusion.

When calculating the dose of neuromuscular blocking agents the following factors must be

taken into account:

The anaesthetic technique used, potential interactions with the drugs used before and

during anaesthesia, and the condition of the individual patient.

The use of an appropriate neuromuscular monitoring technique is recommended to monitor

neuromuscular block and recovery.

Inhalation anaesthetics do potentiate the neuromuscular blocking effects of Norcuron. This

potentiation however, becomes clinically relevant in the course of anaesthesia, when the

volatile agents have reached the tissue concentrations required for this interaction.

Consequently, adjustments with Norcuron should be made by administering smaller

maintenance doses at less frequent intervals or by using lower infusion rates of Norcuron

during longer lasting procedures (longer than 1 hour) under inhalation anaesthesia (see Drug

Interactions).

Initial Dose: 0.10 mg/kg provides good to excellent intubating conditions within 2.5 to 3

minutes.

Incremental doses: 0.02 - 0.04 mg/kg.

Skeletal muscle relaxation (to 25% recovery) lasts for 20-40 minutes after initial or

incremental doses.

With suxamethonium as the intubating agent, initial doses of 0.04-0.06 mg/kg of Norcuron

will produce complete neuromuscular block with a similar duration of clinical effect. If

suxamethonium is used prior to Norcuron the administration of Norcuron should be delayed

until the patient starts recovering from suxamethonium-induced neuromuscular blockade.

The effect of prior use of other non-depolarising neuromuscular blocking agents on the

activity of Norcuron has not been studied.

Use by continuous infusion

Infusion of Norcuron should be initiated only after early evidence of spontaneous recovery

from the loading dose. The infusion of Norcuron should be individualised for each patient.

The rate of administration should be adjusted to maintain twitch response at 10% of control

twitch height or to maintain 1 to 2 responses to train of four stimulation.

In adults, the infusion rate required to maintain neuromuscular block at this level ranges from

0.8 to 1.4

g vecuronium bromide per kg per min. For infants see “Dosage in Children”.

Repeat monitoring of neuromuscular block is recommended since infusion rate requirements

vary from patient to patient and with the anaesthetic method used.

RA 8720 AU S4 (REF 4.0) A140814 V3

Dosage in elderly patients

The same intubation and maintenance doses as for younger adults can be used. However,

the duration of action is prolonged in elderly compared to younger subjects due to changes in

pharmacokinetic mechanisms. The onset time in elderly is similar to younger adults.

Dosage in children

Norcuron is not approved for use in neonates or premature babies. Therefore no dosing

recommendation is made.

Infants under 1 year of age but older than 7 weeks are moderately more sensitive to

Norcuron on a mg/kg basis than adults (See also Precautions, Use in Infants). Since the

onset time of Norcuron in these patients is considerably shorter than in adults and children,

the use of high intubating doses in general is not required for early development of good

intubating conditions. Since the duration of action and recovery time with Norcuron is longer

in infants than in children and adults, maintenance doses are required less frequently.

Dose requirements for children (2 – 10 years) are higher (see Pharmacodynamics).

However, the same intubation and maintenance doses as for adults are usually sufficient.

Since the duration of action is shorter in children, maintenance doses are required more

frequently.

Although there is very little information on dosage in adolescents, it is advised to use the

same dose as in adults, based on the physiological development at this age.

Dosage in overweight and obese patients

When used in overweight or obese patients (defined as patients with a body weight of 30%

or more above ideal body weight), doses should be reduced taking into account an ideal

body weight.

Higher doses

Should there be a reason for selection of larger doses in individual patients, initial doses

ranging from 0.15 mg up to 0.4 mg vecuronium bromide per kg body weight have been

administered for surgery both under halothane and neuroleptic anaesthesia without adverse

cardiovascular effects being noted as long as ventilation is properly maintained. The use of

these high dosages of Norcuron pharmacodynamically decreases the onset time and

increases the duration of action.

Compatibility with Infusions

When Norcuron is reconstituted with water for injections, the resultant solution can be mixed

with the following infusion fluids, packed in PVC or glass, to a dilution up to 40 mg/L:

- 0.9% NaCl solution

- 5% glucose solution

- Ringer’s solution

- Ringer’s solution 2.5% glucose

When reconstituted with water for injections, Norcuron can also be injected into the line of a

running infusion of the following fluids:

- Lactated Ringer’s solution

- Lactated Ringer’s solution and 5% glucose

- 5% glucose and 0.9% NaCl solution

- Haemaccel

- Dextran-40 5% in 0.9% NaCl solution

As is the case for many other drugs, Norcuron has been shown to be incompatible when

added to thiopentone or thiopentone containing solutions.

RA 8720 AU S4 (REF 4.0) A140814 V3

Compatibility studies with other brands of these drugs or with other infusion fluids have not

been performed.

If Norcuron is administered via the same infusion line that is also used for other drugs, it is

important that this infusion line is adequately flushed (e.g. with 0.9 % NaCl) between

administration of Norcuron and drugs for which incompatibility with Norcuron has been

demonstrated or for which compatibility with Norcuron has not been established.

Neither the reconstituted Norcuron in water for injections nor the solutions further diluted with

the compatible infusion fluids contain any antimicrobial preservatives. To avoid microbial

contamination hazards, the reconstituted or further diluted Norcuron injections should be

used immediately after preparation and any residue discarded. Do not use Norcuron when

the solution after reconstitution contains particles or is not clear.

OVERDOSAGE

The possibility of iatrogenic overdosage can be minimised by carefully using an appropriate

neuromuscular monitoring technique.

Clinical Features

The symptoms of overdosage with a non-depolarising muscle relaxant are those of

prolonged paralysis, apnoea, low tidal volume, respiratory depression and/or persistent

muscle weakness. Death may follow acute respiratory failure unless treated promptly.

Management

1) Supportive measures:

Ventilatory support and sedation.

2) Reversal of neuromuscular blockade:

There are two options for the reversal of neuromuscular block: (1) Sugammadex can be

used for reversal of intense (profound) and deep block. The dose of sugammadex to be

administered depends on the level of neuromuscular block. (2) An acetylcholinesterase

inhibitor (e.g pyridostigmine, neostigmine or edrophonium), with appropriate vagolytic (e.g

atropine) can be used at reappearance of T

or at the first signs of clinical recovery and

should be administered in adequate doses. Adequate reversal can be judged by the

ability of the patient to lift his or her head for at least 5 seconds or preferably by the use of

an appropriate neuromuscular monitoring technique. When administration of an

acetylcholinesterase inhibiting agent fails to reverse the neuromuscular effects of

Norcuron, ventilation must be continued until spontaneous breathing is restored.

Overdosage of an acetylcholinesterase inhibitor can be dangerous.

PRESENTATION AND STORAGE CONDITIONS

Norcuron 4mg*

2 mL ampoules each containing 4.0 mg sterile lyophilised vecuronium bromide

Single component: Boxes of 10 ampoules (without solvent).

Composite pack: Boxes of 10 or 50 ampoules with a 1 mL ampoule of solvent (water for

injections) for each ampoule of Norcuron.

Shelf life 3 years when stored below 25

C and protected from light.

*

Presentation not currently marketed in Australia.

RA 8720 AU S4 (REF 4.0) A140814 V3

Norcuron 10mg

5mL vials each containing 10.0 mg sterile lyophilised vecuronium bromide.

Single component: Boxes of 10 vials (without solvent).

Shelf life 2 years when stored below 25

C and protected from light.

NAME AND ADDRESS OF THE SPONSOR

Merck Sharp & Dohme (Australia) Pty Limited

Level 1, Building A

26 Talavera Road

Macquarie Park, NSW 2113

Australia

POISON SCHEDULE OF THE MEDICINE

S4 - Prescription Only Medicine

DATE OF APPROVAL

Date of TGA Approval: 23 December 2010

Date of most recent amendment: 17 September 2014